Endosomal recognition of viral single stranded (ss) RNA and imidazoquinoline compounds occurs by means of TLR7 and TLR8. Structural analyses have revealed that both TLR7 and TLR8 possess two binding sites which do not share the same specificities (Zhang Z et al. 2016). The binding site 1 is highly conserved between TLR7 and TLR8 and binds nucleosides (guanosine (G) for TLR7 and uridine (U) for TLR8) or base analogs. Binding site 2 of TLR7 and TLR8 is less conserved and binds ssRNA with U(U) and U(G) motifs. TLR7 acts as a dual receptor for G and U-containing ssRNAs. Binding of ssRNA to the site 2 of TLR7 strongly enhances the interaction of TLR7 and G at the first site leading to subsequent receptor dimerization. Conversely, chemical ligands are adequately potent to induce TLR7 dimerization by binding to the first site alone (Zhang Z et al. 2016, 2018). Further, upon ligand stimulation, the TLR8 dimer was reorganized such that the two C termini were brought into proximity (Tanji H et al. 2013). The loop between leucine-rich repeat 14 (LRR14) and LRR15 was cleaved; however, the N- and C-terminal halves remained associated and contributed to ligand recognition and dimerization, which enables downstream signaling processes (Tanji H et al. 2013, 2016).
Diebold, SS, Kaisho, T, Hemmi, H, Akira, S, Reis e Sousa, C
Jurk, M, Heil, F, Vollmer, J, Schetter, C, Krieg, AM, Wagner, H, Lipford, G, Bauer, S
Li, Y, Chen, M, Cao, H, Zhu, Y, Zheng, J, Zhou, H
Hemmi, H, Kaisho, T, Takeuchi, O, Sato, S, Sanjo, H, Hoshino, K, Horiuchi, T, Tomizawa, H, Takeda, K, Akira, S
Heil, F, Hemmi, H, Hochrein, H, Ampenberger, F, Kirschning, C, Akira, S, Lipford, G, Wagner, H, Bauer, S
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